The Mayer–Rokitansky–Kuster–Hauser syndrome (MRKH syndrome), simply called Rokitansky syndrome or vaginal aplasia of the uterus, is a congenital condition that is characterized by the absence of the uterus and vagina, but ovaries are present and the external genitalia are normal. It affects at least 1 out of 4500 women. MRKH may be isolated (Type I), but it is more frequently associated with renal, vertebral, and to a lesser extent, auditory and cardiac defects (MRKH Type II or Mullerian duct aplasia, Renal dysplasia, and Cervical Somite anomalies association - mullerian duct aplasia, renal dysplasia, and cervical somite anomalies). There were very few cases of MRKH syndrome reported in the literature. Here, we report two cases of MRKH syndrome, one in a 20-year-old woman who presented with primary amenorrhea (MRKH Type I) and the other in a 65-year-old woman with primary amenorrhea and associated renal malformations and a rare ovarian sertoliform variant of endometrioid tumor (MRKH Type II).

Mayer–Rokitansky–Kuster–Hauser syndrome (MRKH syndrome) is named after its most famous discoverer Baron Karl von Rokitansky (Czechoslovakia, 1804–1878), a physician and professor at the University of Vienna. In 1829 and in 1838, Mayer–Rokitansky described a syndrome that includes agenesis of the uterus and vagina, while Kuster then observed a correlation with urological defects. For this reason, this condition is also known as MRKH syndrome. Type I (isolated) MRKH is less frequent than Mullerian duct aplasia, Renal dysplasia, and Cervical Somite anomalies (MURCS) association. Polycystic ovaries and ovarian tumors have been described in association with MRKH Type II. Here, we are reporting an isolated uterovaginal aplasia and MRKH associated with a very rare sertoliform variant of endometrioid carcinoma of the ovary.[1]

Case Reports

Case 1

A 20-year-old nulliparous woman came with the complaints of swelling and periodic pain in the right groin for 2 months. She had the swelling in the left groin for 8 years, which was gradually increasing in size. She did not attain menarche. She got married and her marital life is 1 year. Gynecologists examined the case and they found bilateral inguinal swellings on examination. Uterus could not be felt in per vaginal and per speculum examinations. Surgeons diagnosed the case as bilateral irreducible sliding inguinal hernia. Ultrasonography and contrast-enhanced computerized tomography findings showed that the uterus was absent with nonvisualization of the ovaries in the ovarian fossa, and oval, well-defined mixed echogenic masses were noted in the inguinal regions. Kidney and urinary bladder appeared normal. External female genitalia were noted. Clitoromegaly was observed. Buccal smear was positive for Barr body and showed single Barr body in 40% of the cells. Karyotype was 46, XX (female). Hormonal study for follicle-stimulating hormone and luteinizing hormone was within normal limits. Intraoperatively, bilateral indirect inguinal hernia with ovary and fallopian tubes as content was identified. The right oophorectomy with bilateral hernioplasty was done [Figure 1]. On macroscopic examination, there was an irregular, gray-brown specimen with attached tube measuring 7.5 cm × 6.5 cm × 3 cm. Cut section showed necrotic ovarian tissue (5.5 cm × 3 × 1.5 cm) with predominantly cystic area and small solid gray-white area (3.5 cm × 2 cm × 1 cm) and attached fallopian tube with fimbrial end measuring 9 cm in length. Microscopically, sections showed functioning ovarian stroma with hemorrhagic corpus luteum and corpora albicantia. Sections from fallopian tube showed normal luminal plicae [Figure 2]. Based on clinical features, radiological, biochemical, and histopathological examinations, our first case was diagnosed as MRKH syndrome Type 1.

A 65-year-old unmarried, nulliparous woman with primary amenorrhea and absent uterus came with a complaint of abdominal pain for 1 month. She is hypertensive, having bilateral ectopic pelvic kidneys and left ovarian mass. She did not attain menarche. On examination, mobile, cystic mass of 12 cm × 10 cm was noted in the left iliac fossa. Uterus and vagina were absent. Sonography was advised and findings revealed that liver is in normal size and echogenicity. The right kidney measuring 7.8 cm × 3.2 cm and the left kidney measuring 8.3 cm × 4.4 cm were located in the pelvis. Uterus was not seen. A 10 cm × 9 cm mass lesion with solid and cystic component with minimal internal vascularity possibly of ovarian origin was noted in the left adnexa [Figure 3]. There was no history of any previous surgeries. Exploratory laparotomy and the left oophorectomy were done. Intraoperative findings were absence of uterus and ectopic kidneys in the right and left iliac fossa. The right ovary was not visualized. The left ovarian mass of size 8 cm×7cm was identified, while removing it was ruptured and the tissue was sent to histopathology [Figure 3]. Sections showed highly cellular tumor tissue composed of extensive solid areas of compact, anastomosing cords of cells with stratified appearance. In-between the solid areas, tubules, acini, and papillary structures were noted which are lined by columnar cells with elongated nuclei. Extensive areas of congestion and brisk mitotic activity (2–3/hpf) were observed. Based on these features, a final diagnosis of sertoliform variant of endometrioid carcinoma of ovary associated with MRKH syndrome (Type II) was made [Figure 4].

Figure 3: (a) Radiological images of a 65-year-old woman with Mayer–Rokitansky–Kuster–Hauser Type II. (b and c) Intraoperative and gross pictures of the left ovarian mass

MRKH syndrome is subdivided into two types: type I (isolated) or Rokitansky sequence (OMIM 277000) and Type II or MURCS association (OMIM 601076).[1] MRKH syndrome is the second most common cause of primary amenorrhea after gonadal pathology.[2] The first sign of MRKH syndrome is a primary amenorrhea in young women presenting otherwise with normal development of the secondary sexual characteristics and normal external genitalia, normal and functional ovaries, and karyotype 46, XX, without visible chromosomal anomaly. In our study, both cases presented with primary amenorrhea with MRKH syndrome (Mullerian agenesis), a type of developmental anomaly.[1]

Considering the clinical features, absence of uterus and vagina with nonvisualization of ovaries in the ovarian fossa and normally functioning ovary and fallopian tube as contents of the right inguinal hernia, a final diagnosis of MRKH syndrome (Type I) was made in the first case.

Associated upper urinary tract malformations are found in about 40% of the cases with MRKH syndrome. Predominantly, they include unilateral renal agenesis (23–28%), ectopia of one or both kidneys (17%), renal hypoplasia (4%), horseshoe kidney, and hydronephrosis. Auditory defects or deafness are associated with 10–25% of the MURCS patients. Associated skeletal abnormalities of the spine are found in 30–40% of the cases. The association of MRKH with heart malformations is less common. Cases of polycystic ovaries and ovarian tumors have been described in women presenting otherwise with normal 46, XX karyotype.[3],[4],[5],[6],[7],[8],[9] No single case of sertoliform endometrioid carcinoma associated with MRKH syndrome is reported in the literature.

Our second case presented with primary amenorrhea, absence of uterus and vagina, bilateral pelvic ectopic kidneys (MRKH syndrome Type II), and a very rare sertoliform variant of endometrioid carcinoma of the left ovary.

Sertoliform endometrioid carcinoma of the ovary (SEC) was reported previously in the literature. Since then, only single additional case series has been published. Two case reports have also been published. SEC of the ovary is an uncommon variant that bears histologic similarity to Sertoli–Leydig cell tumors.[10]

When physical examination findings are consistent with the absent or hypoplastic vagina, the immediate differential diagnosis includes MRKH and complete androgen insensitivity syndrome, which is characterized by genotype XY, normal male testosterone levels, decreased pubic and axillary hair, and presence of intra-abdominal testicles.[11]

Conclusion

The phenotypic manifestations of MRKH overlap with various other syndromes or associations. Hence, all women with primary amenorrhea should undergo a complete investigation of both the genital tract and the endocrine system. These case reports emphasize that SEC of the ovary is an exceptionally rare association with MRKH Type II.